Laboratory of Systems Cancer Biology, Rockefeller University, New York, NY 10065, USA.
Genes Dev. 2011 Feb 1;25(3):226-31. doi: 10.1101/gad.1974211.
Post-transcriptional regulators have emerged as robust effectors of metastasis and display deregulated expression through unknown mechanisms. Here, we reveal that the human microRNA-335 locus undergoes genetic deletion and epigenetic promoter hypermethylation in every metastatic derivative obtained from independent patients' malignant cell populations. Genetic deletion of miR-335 is a common event in human breast cancer, is enriched for in breast cancer metastases, and also correlates with ovarian cancer recurrence. We furthermore identify miR-335 as a robust inhibitor of tumor reinitiation. We thus implicate the miR-335 locus on 7q32.2 as the first selective metastasis suppressor and tumor initiation suppressor locus in human breast cancer.
转录后调控因子已成为转移的有效调节剂，并通过未知机制显示出失调的表达。在这里，我们揭示了人类 microRNA-335 基因座在每个来自独立患者恶性细胞群体的转移性衍生体中经历遗传缺失和表观遗传启动子超甲基化。miR-335 的遗传缺失是人类乳腺癌中的常见事件，在乳腺癌转移中富集，并且还与卵巢癌复发相关。我们进一步将 miR-335 鉴定为肿瘤再起始的有效抑制剂。因此，我们将 7q32.2 上的 miR-335 基因座作为人类乳腺癌中第一个选择性转移抑制因子和肿瘤起始抑制因子基因座。
